Born and raised in Saratoga Springs, New York, Pierce began acting in high school and attended Yale University, where he majored in English and theater. Pierce held an assortment of jobs, incuding security guard and tie salesman in New York City before breaking into film in the late 1980s. Because of his resemblance to Kelsey Grammer, the role of Niles Crane on the Cheers spin-off Frasier was created for him; for this role, Pierce was nominated for a Best Supporting Actor Emmy for a record ten consecutive years, winning in 1995, 1998, and 1999.